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Grapefruit and Antidepressants: Interaction Explained

Vicky Davis, FNP

Reviewed by Vicky Davis, FNP

Written by Rachel Sacks

Published 02/25/2023

Grapefruit and antidepressants — maybe not the most likely of combinations but there’s more you should know about this pairing.

While grapefruit is a delicious and nutritious fruit with health benefits, the citrus fruit as well as its juice can interact with common medications — namely, antidepressants.

You might be wondering why this interaction happens. How dangerous is it to mix grapefruit juice and antidepressants? Is combining grapefruit and antidepressants fatal?

If you’re currently undergoing treatment with antidepressants, keep reading to learn why these medications have a warning label for grapefruit and to know more about the interaction between grapefruit and antidepressants.

Before diving into why grapefruit and antidepressants interact the way they do, knowing what antidepressants are and what they do is helpful.

If you deal with depression or an anxiety disorder, treatment with antidepressants is one of the most common options.

How does treatment with antidepressants help depression? Well, it involves the brain. Depression is thought to be tied to low levels of certain neurotransmitters in your brain — chemicals that transfer information between neurons. Serotonin, norepinephrine and dopamine are the most talked about chemicals regarding depression.

Antidepressants increase the levels of serotonin, norepinephrine, dopamine or other chemicals in your brain by blocking them from being reabsorbed.

There are many different types of antidepressants available. Some of the most common antidepressants include:

  • Selective serotonin reuptake inhibitors (SSRIs).SSRIs are the most commonly prescribed antidepressant due to their tolerable side effects.

  • Serotonin-norepinephrine reuptake inhibitors (SNRIs). These antidepressants are also a fairly common treatment. In addition to serotonin, they also stop norepinephrine from being reabsorbed. Duloxetine and venlafaxine are two common SNRIs.

  • Monoamine oxidase inhibitors (MAOIs). An older type of drug, treatment with antidepressants of this class isn’t as common anymore due to strong side effects.

Our full antidepressants list goes into more detail about the different types of medications, what they treat, their side effects and more.

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You may want to hold off on consuming grapefruit while taking antidepressants until you know what side effects your medication causes. A potentially dangerous drug interaction can happen between antidepressants and grapefruit.

But why do these two even interact at all, and what is the potential interaction?

While researchers aren’t sure exactly which of grapefruit’s hundred or so chemicals causes the interaction, one, in particular, is thought to play a role. The chemical furanocoumarin — which is also found in other citrus juices like tangelos — doesn’t interact directly with antidepressant medication but instead binds to an enzyme in the intestinal tract.

When the cytochrome P450 enzymes — also referred

to as CYP3A4 — bind to furanocoumarin, this can reduce the absorption of certain medications. Grapefruit in any form (freshly squeezed juice, frozen concentrate or whole fruit) can reduce the activity of cytochrome P450 enzymes.

By blocking the cytochrome P450 enzymes, grapefruit makes it easier for medication to pass from the gut to the bloodstream, which can raise blood levels to abnormally high and even dangerous levels.

The grapefruit interaction prevents the cytochrome P450 enzymes from breaking down the medication, taking 36 hours or more to do so. This can lead to the medication staying in your system for much longer, with the effects being similar to an overdose.

Research suggests that certain antidepressants — such as sertraline, fluoxetine, fluvoxamine, paroxetine and Wellbutrin — may have a potential i

nteraction with grapefruit.

The grapefruit interaction with sertraline could be particularly harmful. Older research suggests that eating grapefruit while on sertraline can lead to too much sertraline in the blood.

High levels of sertraline could increase the experience of side effects like dizziness or drowsiness.

But is the combination of grapefruit and antidepressants fatal?

The medication’s interaction with grapefruit causes the drug to stay in your system longer, similar to an overdose. Fatal overdoses on antidepressants are less common, however.

Grapefruit juice doesn’t affect all antidepressants. A severe interaction with grapefruit depends on the person, the amount of grapefruit juice and the antidepressant. While there’s not always an interaction between grapefruit juice and antidepressants, it’s best to ask your healthcare provider if grapefruit is alright to eat while taking your medication.

It should also be noted that studies have found that a single glass of grapefruit juice or other citrus juices can also interact with other medications and affect blood levels. Some other medications that can have similar interactions with grapefruit are:

  • Statin drugs that lower cholesterol

  • High blood pressure medications

  • Anti-anxiety drugs

  • Antihistamines

  • Drugs that treat abnormal heart rhythms

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While grapefruit and grapefruit juice certainly have their health benefits, the interaction between antidepressants and grapefruit can increase the medication's strength to sometimes dangerous levels.

This is due to grapefruit juice blocking the medication from properly metabolizing and instead absorbing into the bloodstream, raising your blood level very quickly. This may also cause there to be too much of the medication in your system, leading to an overdose effect. However, an overdose on antidepressants is rarely fatal.

So while it’s not fatal, you may want to think twice about washing down your antidepressants with grapefruit juice. If you’re concerned about what can interact with your medication, consult with a licensed psychiatrist.

11 Sources

Hims & Hers has strict sourcing guidelines to ensure our content is accurate and current. We rely on peer-reviewed studies, academic research institutions, and medical associations. We strive to use primary sources and refrain from using tertiary references.

  1. Grapefruit Juice and Some Drugs Don't Mix. (2021, July 1). FDA. Retrieved from https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix
  2. Winerman, L. (2017, November 1). By the numbers: Antidepressant use on the rise. American Psychological Association. Retrieved from https://www.apa.org/monitor/2017/11/numbers
  3. Garcia, D. (2015, December 22). Happy or SAD: The chemistry behind depression. The Jackson Laboratory. Retrieved from https://www.jax.org/news-and-insights/jax-blog/2015/december/happy-or-sad-the-chemistry-behind-depression
  4. Antidepressants. (2022, January 26). MedlinePlus. Retrieved from https://medlineplus.gov/antidepressants.html
  5. Grapefruit and medication: A cautionary note. (n.d.). Harvard Health. Retrieved from https://www.health.harvard.edu/staying-healthy/grapefruit-and-medication-a-cautionary-note
  6. Bailey, D. G., Dresser, G., & Arnold, M. O. (2013). Grapefruit–medication interactions: Forbidden fruit or avoidable consequences? CMAJ : Canadian Medical Association Journal, 185(4), 309-316. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589309/
  7. Grapefruit and Medicines: Can They Mix? (n.d.). Poison Control. Retrieved from https://www.poison.org/articles/grapefruit-and-medicines
  8. Richelson, E. (1997). Pharmacokinetic Drug Interactions of New Antidepressants: A Review of the Effects on the Metabolism of Other Drugs. Mayo Clinic Proceedings, 72(9), 835-847. Retrieved from https://www.sciencedirect.com/science/article/abs/pii/S002561961163499X
  9. Lee, A. J., Chan, W. K., Harralson, A. F., Buffum, J., & Bui, B. C. (1999). The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study. Clinical Therapeutics, 21(11), 1890-1899. Retrieved from https://www.sciencedirect.com/science/article/abs/pii/S0149291800867375
  10. Overdose Death Rates | National Institute on Drug Abuse. (2022, January 20). National Institute on Drug Abuse. Retrieved from https://nida.nih.gov/research-topics/trends-statistics/overdose-death-rates
  11. Kiani, J., & Imam, S. Z. (2006). Medicinal importance of grapefruit juice and its interaction with various drugs. Nutrition Journal, 6, 33. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2147024/

This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment. Learn more about our editorial standards here.

Vicky Davis, FNP

Dr. Vicky Davis is a board-certified Family Nurse Practitioner with over 20 years of experience in clinical practice, leadership and education. 

Dr. Davis' expertise include direct patient care and many years working in clinical research to bring evidence-based care to patients and their families. 

She is a Florida native who obtained her master’s degree from the University of Florida and completed her Doctor of Nursing Practice in 2020 from Chamberlain College of Nursing

She is also an active member of the American Academy of Nurse Practitioners.

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